Coexistence of Aflatoxicosis with Protein Malnutrition Worsens Hepatic Oxidative Damage in Rats.

To investigate the effects of the coexistence of aflatoxin B1 (AFB1) and protein malnutrition in rat liver, weanling rats were fed either normal protein diet (20% protein), low-protein (PEM) diet (5%), normal protein diet + 40 ppb AFB1, or low-protein diet + 40 ppb AFB1. After 8 weeks, biomarkers of hepatic functions and oxidative stress, caspase-3 activity, and tumor suppressor protein 53 (p53) were determined spectrophotometrically. Randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) was employed to determine genomic alterations among the groups. Coexistence of aflatoxicosis and PEM significantly decreased glutathione, glutathione-S-transferase, glutathione peroxidase, and superoxide dismutase, while it increased peroxidase and catalase. RAPD-PCR showed genomic alterations that were associated with significant increases in p53 level and caspase-3 activity in rats fed PEM diet + AFB1. In conclusion, the coexistence of aflatoxicosis and protein malnutrition induced oxidative stress with concomitant genomic alterations in the liver of weanling rats.

Hesperidin prevents lipopolysaccharide-induced endotoxicity in rats.

CONTEXT: Lipopolysaccharide (LPS) is a major trigger of septic shock resulting in multiple organ damage through excessive stimulation of the host's immune cells resulting in the release of cytokines. Previous studies have shown that hesperidin has several beneficial properties against inflammation and oxidative stress. OBJECTIVE: The influence of hesperidin on endotoxemia, endothelial dysfunction, inflammation, and oxidative stress was investigated using a murine model of sepsis. MATERIALS AND METHODS: Rats were pretreated for 15 d with three doses (50 mg/kg, 100 mg/kg, and 200 mg/kg) of hesperidin prior to LPS administration. Afterwards, the levels of biomarkers of endotoxemia, endothelial dysfunction, and oxidative stress were assessed. Reverse transcriptase PCR technique was used to assess the expression of hepatic proinflammatory cytokines. RESULTS: Hesperidin pretreatment significantly (p < 0.05) reduced circulating endotoxin, as well as the levels of bactericidal permeability increasing protein and procalcitonin, and the associated endothelial dysfunction by reducing the levels of plasma soluble intercellular adhesion molecules 1 and inducible nitric oxide (iNO) synthase. There was also down-regulation of the expression of gene for interleukin 1α, interleukin 1ß, interleukin 1 receptor, interleukin 6, and tumor necrosis factor α (TNFα) in the liver of rats treated with LPS as a result of hesperidin pretreatment. Hesperidin also showed anti-oxidative properties through the significant (p < 0.05) reduction of NO, hydroperoxides, and thiobarbituric acid reactive substances and increase of glutathione, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase in the organs. CONCLUSION: Different doses of hesperidin can prevent endotoxemia-induced oxidative stress as well as inflammatory and endothelial perturbation in rats when administered for as few as 15 d before exposure to endotoxin.

Early-life AFB1 exposure: DNA methylation and hormone alterations.

Aflatoxins are secondary metabolites of mold that contaminate food and feedstuff. They are found in various food including grains, nuts, milk and eggs. Aflatoxin B1 (AFB1) is the most poisonous and commonly found of the various types of aflatoxins. Exposures to AFB1 start early in life viz. in utero, during breastfeeding, and during weaning through the waning foods which are mainly grain based. Several studies have shown that early-life exposures to various contaminants may have various biological effects. In this chapter, we reviewed the effects of early-life AFB1 exposures on changes in hormone and DNA methylation. In utero AFB1 exposure results in alterations in steroid and growth hormones. Specifically, the exposure results in a reduction in testosterone levels later in life. The exposure also affects the methylation of various genes that are significant in growth, immune, inflammation, and signaling pathways.

Breast Cancer Phenotypes in Africa: A Scoping Review and Meta-Analysis.

PURPOSE: Africans have been associated with more aggressive forms of breast cancer (BC). However, there is a lack of data regarding the incidence and distribution of different subtypes on the basis of phenotypic classification. This scoping review and meta-analysis was undertaken to determine the distribution pattern of BC phenotypes (luminal, human epidermal growth factor receptor 2 [HER2]+, and triple-negative breast cancer [TNBC]) across the African region. METHODS: Four online databases (PubMed, Scopus, ProQuest, and EBSCOhost) were accessed to identify studies published between 2000 and 2022 reporting the representation of receptor status (estrogen receptor, progesterone receptor, and HER2) in African patients with BC. Furthermore, the meta-analysis was carried out using a random-effects model and pooled using the inverse variance method and logit transformation. 95% CI and I2 statistics were calculated using the Clopper-Pearson method to estimate between-study heterogeneity. RESULTS: A total of 2,734 records were retrieved, of which 2,133 were retained for further screening. After the screening, 63 studies were finally selected for the scoping review and meta-analysis. The pooled frequency of luminal, HER2-positive (HER2+), and TNBC was estimated at 56.30%, 12.61%, and 28.10%, respectively. Northern Africa had the highest frequency of the luminal subtype, while West Africa showed higher frequencies of HER2+ and TNBC subtypes. The review also had a representation of only 24 countries in Africa. CONCLUSION: Our results highlight the disparity in the representation of molecular subtypes among the people in different regions of Africa. There is a need to incorporate routine molecular subtyping into the management of African patients with BC.

Haptoglobin genotypes and malaria comorbidity in breast cancer and healthy Nigerian women.

Background: Breast cancer is the leading cause of mortality among women, with over a million cases recorded globally. Haptoglobin (Hp) protein and genotypes play important roles in cancer predisposition and progression, but studies have reported varying outcomes in populations. Aim: The association of Hp genotypes in breast cancer patients with malaria has not been investigated in Nigerians, which is the aim of our study. In healthy women (control; n = 279) and clinically diagnosed breast cancer patients (breast cancer; n = 70). Methods: Haptoglobin genotypes and Plasmodium falciparum cyclooxygenase III genes were detected by polymerase chain reaction (PCR). Proportions were compared, and the test of association was carried out with a significance level set at P < 0.05. Results: Overall, 311 of 349 (89%) individuals had malaria infection with similar proportions in breast cancer (63 of 70) and healthy control group (248 of 279); malaria incidence was, however, lower in Hp 2-2 breast cancer patients (P = 0.04). The prevalence of Hp genotypes was Hp 1-1 (78.2%), Hp 2-1 (7.2%), and 2-2 (14.6%). In breast cancer groups, Hp 2-2 genotype was significantly lower with 3 (4.2%) of 70 vs. 48 (17.2%) of 279 in control group (P = 0.006). Conclusions: The results of the study show low Hp 2-2 genotype relative to other genotypes in breast cancer patients; we conclude that low Hp 2-2 genotype is associated with lower malaria risk in breast cancer Nigerian women. It is important to further understand the roles malaria, Hp, and other genotypes play in the pathogenesis of aggressive breast cancer commonly seen in Nigerian women.

Résumé Contexte: Le cancer du sein est la principale cause de mortalité chez les femmes, avec plus d'un million de cas enregistrés dans le monde. La protéine et les génotypes de l'haptoglobine (Hp) jouent un rôle important dans la prédisposition et la progression du cancer, mais des études ont rapporté des résultats variables dans les populations. Objectif: L'association des génotypes d'haptoglobine chez les patientes atteintes d'un cancer du sein et atteintes de paludisme n'a pas été étudiée chez les Nigérians, ce qui est l'objectif de notre étude. Chez les femmes en bonne santé (témoin ; nombre = 279) et les patientes atteintes d'un cancer du sein diagnostiqué cliniquement (cancer du sein ; nombre = 70). Méthodologie: Les génotypes de l'haptoglobine et les gènes de la cyclooxygénase-III de Plasmodium falciparum ont été détectés par PCR. Les proportions ont été comparées et le test d'association a été réalisé avec un seuil de signification fixé à P < 0,05. Résultats: Dans l'ensemble, 311 personnes sur 349 (89 %) avaient une infection palustre avec des proportions similaires dans le groupe du cancer du sein (63 sur 70) et dans le groupe témoin sain (248 sur 279); l'incidence du paludisme était cependant plus faible chez les patientes atteintes d'un cancer du sein Hp 2-2 (p = 0,04). La prévalence des génotypes Hp était : Hp 1-1 (78,2 %), Hp 2-1 (7,2 %) et 2-2 (14,6 %). Dans les groupes de cancer du sein, le génotype Hp 2-2 était significativement plus faible avec 3 (4,2 %) sur 70 contre 48 (17,2 %) sur 279 dans le groupe témoin (p = 0,006). Conclusions: Les résultats de l'étude montrent un faible génotype Hp 2-2 par rapport aux autres génotypes chez les patientes atteintes d'un cancer du sein; nous concluons qu'un faible génotype Hp 2-2 est associé à un risque de paludisme plus faible chez les femmes nigérianes atteintes d'un cancer du sein. Il est important de mieux comprendre les rôles que jouent le paludisme, l'haptoglobine et d'autres génotypes dans la pathogenèse du cancer du sein agressif couramment observé chez les femmes nigérianes. Mots-clés: Cancer du sein, génotypes, haptoglobine, paludisme, Nigeria.

Authorship Patterns in Cancer Genomics Publications Across Africa.

PURPOSE: Authorship is a proxy indicator of research capacity. Understanding the research capacity is imperative for developing population-specific cancer control strategies. This is particularly apropos for African nations, where mortality from cancer is projected to surpass that from infectious disease and the populations are critically under-represented in cancer and genomics studies. Here, we present an analysis and discussion of the patterns of authorship in Africa as they pertain to cancer genomics research across African countries. METHODS: PubMed metadata of relevant cancer genomics peer-reviewed publications on African populations, published between January 1, 1990, and December 31, 2019, were retrieved and analyzed for patterns of authorship affiliation using R packages, RISmed, and Pubmed.mineR. RESULTS: The data showed that only 0.016% (n = 375) of cancer publications globally were on cancer genomics of African people. More than 50% of the first and last authors of these publications originated from the North African countries of Tunisia, Morocco, Egypt, and Algeria. South Africa (13.6% and 12.7%) and Nigeria (2.2% and 1.9%) were the Sub-Saharan African countries most represented by first and last authorship positions, respectively. The United States contributed 12.6% of first and last authored papers, and nearly 50% of all African countries had no contributing author for the publications we reviewed. CONCLUSION: This study highlights and brings awareness to the paucity of cancer genomics research on African populations and by African authors and identifies a need for concerted efforts to encourage and enable more research in Africa, needed for achieving global equity in cancer outcomes.

Vitamin D: Possible Therapeutic Roles in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a unique type of liver cancer instigated by underlying liver diseases. Pre-clinical evidence suggests that HCC progression, like other cancers, could be aided by vitamin D deficiency. Vitamin D is a lipid-soluble hormone usually obtained through sunlight. Vitamin D elucidates its biological responses by binding the vitamin D receptor; thus, promoting skeletal mineralization, and maintain calcium homeostasis. Other reported Vitamin D functions include specific roles in proliferation, angiogenesis, apoptosis, inflammation, and cell differentiation. This review highlighted studies on vitamin D's functional roles in HCC and discussed the specific therapeutic targets from various in vivo, in vitro and clinical studies over the years. Furthermore, it described recent advancements in vitamin D's anticancer effects and its metabolizing enzymes' roles in HCC development. In summary, the review elucidated specific vitamin D-associated target genes that play critical functions in the inhibition of tumorigenesis through inflammation, oxidative stress, invasion, and apoptosis in HCC progression.

Bisphenol A in Africa: A review of environmental and biological levels.

Bisphenol A (BPA) is a synthetic ubiquitous environmental toxicant present in many industrial and consumer products. BPA is recognized as an endocrine-disrupting chemical (EDC), and its mechanisms of perturbation of the physiological process include interference with hormone pathways and epigenetic modifications. An increase in industrial productions and food packaging across Africa has resulted in increased utilization of BPA-containing products with a concomitant increase in environmental bioaccumulation and human exposure. In order to assess the extent of this bioaccumulation, we identified, collated, and summarized the levels of BPA that have been reported across Africa. To achieve this aim, we performed a systematic search of four indexing databases to identify articles and extracted the necessary data from the selected articles. Of the 42 publications we retrieved, 42% were on water samples, 22% on food, 20% on human biological fluids, 10% on sediments, soils, and sludge and 6% on consumer and personal care products (PCPs). The highest level of BPA reported in literature across Africa was 251 ng/mL, 384.8 ng/mL, 937.49 ng/g, 208.55 ng/mL, 3,590 µg/g, and 154,820 µg/g for water, wastewater, food, biological fluids, consumer and PCPs, and semisolids, respectively. This review presented a comparative perspective of these levels relative to regulatory limits and levels reported from other continents. Finally, this review highlighted critical needs for the regulation of BPA across Africa in order to stem its environmental and toxicological impact. We hope that this review will stimulate further research in understanding the impact of BPA on health outcomes and wellbeing across Africa.

Early Life Exposure to Aflatoxin B1 in Rats: Alterations in Lipids, Hormones, and DNA Methylation among the Offspring.

Aflatoxins are toxic compounds produced by molds of the Aspergillus species that contaminate food primarily in tropical countries. The most toxic aflatoxin, aflatoxin B1 (AFB1), is a major cause of hepatocellular carcinoma (HCC) in these countries. In sub-Saharan Africa, aflatoxin contamination is common, and perinatal AFB1 exposure has been linked to the early onset of HCC. Epigenetic programming, including changes to DNA methylation, is one mechanism by which early life exposures can lead to adult disease. This study aims to elucidate whether perinatal AFB1 exposure alters markers of offspring health including weight, lipid, and hormone profiles as well as epigenetic regulation that may later influence cancer risk. Pregnant rats were exposed to two doses of AFB1 (low 0.5 and high 5 mg/kg) before conception, throughout pregnancy, and while weaning and compared to an unexposed group. Offspring from each group were followed to 3 weeks or 3 months of age, and their blood and liver samples were collected. Body weights and lipids were assessed at 3 weeks and 3 months while reproductive, gonadotropic, and thyroid hormones were assessed at 3 months. Prenatal AFB1 (high dose) exposure resulted in significant 16.3%, 31.6%, and 7.5% decreases in weight of the offspring at birth, 3 weeks, and 3 months, respectively. Both doses of exposure altered lipid and hormone profiles. Pyrosequencing was used to quantify percent DNA methylation at tumor suppressor gene Tp53 and growth-regulator H19 in DNA from liver and blood. Results were compared between the control and AFB1 exposure groups in 3-week liver samples and 3-week and 3-month blood samples. Relative to controls, Tp53 DNA methylation in both low- and high-dose exposed rats was significantly decreased in liver samples and increased in the blood (p < 0.05 in linear mixed models). H19 methylation was higher in the liver from low- and high-exposed rats and decreased in 3-month blood samples from the high exposure group (p < 0.05). Further research is warranted to determine whether such hormone, lipid, and epigenetic alterations from AFB1 exposure early in life play a role in the development of early-onset HCC.

A Review of Cancer Genetics and Genomics Studies in Africa.

Cancer is the second leading cause of death globally and is projected to overtake infectious disease as the leading cause of mortality in Africa within the next two decades. Cancer is a group of genomic diseases that presents with intra- and inter-population unique phenotypes, with Black populations having the burden of morbidity and mortality for most types. At large, the prevention and treatment of cancers have been propelled by the understanding of the genetic make-up of the disease of mostly non-African populations. By the same token, there is a wide knowledge gap in understanding the underlying genetic causes of, and genomic alterations associated with, cancer among black Africans. Accordingly, we performed a review of the literature to survey existing studies on cancer genetics/genomics and curated findings pertaining to publications across multiple cancer types conducted on African populations. We used PubMed MeSH terms to retrieve the relevant publications from 1990 to December 2019. The metadata of these publications were extracted using R text mining packages: RISmed and Pubmed.mineR. The data showed that only 0.329% of cancer publications globally were on Africa, and only 0.016% were on cancer genetics/genomics from Africa. Although the most prevalent cancers in Africa are cancers of the breast, cervix, uterus, and prostate, publications representing breast, colorectal, liver, and blood cancers were the most frequent in our review. The most frequently reported cancer genes were BRCA1, BRCA2, and TP53. Next, the genes reported in the reviewed publications' abstracts were extracted and annotated into three gene ontology classes. Genes in the cellular component class were mostly associated with cell part and organelle part, while those in biological process and molecular function classes were mainly associated with cell process, biological regulation, and binding, and catalytic activity, respectively. Overall, this review highlights the paucity of research on cancer genomics on African populations, identified gaps, and discussed the need for concerted efforts to encourage more research on cancer genomics in Africa.

Epigenetic modifications associated with in utero exposure to endocrine disrupting chemicals BPA, DDT and Pb.

Endocrine disrupting chemicals (EDCs) are xenobiotics which adversely modify the hormone system. The endocrine system is most vulnerable to assaults by endocrine disruptors during the prenatal and early development window, and effects may persist into adulthood and across generations. The prenatal stage is a period of vulnerability to environmental chemicals because the epigenome is usually reprogrammed during this period. Bisphenol A (BPA), lead (Pb), and dichlorodiphenyltrichloroethane (DDT) were chosen for critical review because they have become serious public health concerns globally, especially in Africa where they are widely used without any regulation. In this review, we introduce EDCs and describe the various modes of action of EDCs and the importance of the prenatal and developmental windows to EDC exposure. We give a brief overview of epigenetics and describe the various epigenetic mechanisms: DNA methylation, histone modifications and non-coding RNAs, and how each of them affects gene expression. We then summarize findings from previous studies on the effects of prenatal exposure to the endocrine disruptors BPA, Pb and DDT on each of the previously described epigenetic mechanisms. We also discuss how the epigenetic alterations caused by these EDCs may be related to disease processes.

Time-Course Effects of Acute Aflatoxin B1 Exposure on Hepatic Mitochondrial Lipids and Oxidative Stress in Rats.

Aflatoxins are secondary metabolites of certain Aspergillus species, that contaminate staple foods, particularly in developing countries. Aflatoxin B1 (AFB1) is the most toxic and common of the major types of aflatoxins. AFB1 is hepatotoxic and has been implicated in increasing the risk of hepatocellular carcinoma (HCC). We have previously shown that subacute exposure to AFB1 for 7 days disrupts hepatic lipids; therefore, this study determined the time-course effects of acute aflatoxin exposure on hepatic mitochondrial lipids and oxidative stress. To achieve this, thirty male albino rats were randomly assigned to six groups. The groups received an oral dose of 1 mg/kg body weight AFB1 or vehicle only (controls) for one, four, or seven days, respectively. Twenty-four hours after the last dose, the animals were sacrificed and liver excised. Mitochondria and cytosolic fractions were obtained from the liver after which lipids (cholesterol, triacylglycerols) were determined in the mitochondria while biomarkers of oxidative stress (glutathione, glutathione transferase (GST), glutathione peroxidase (GPx), glutathione reductase, nitric oxide (NO), malonaldehyde (MDA), thioredoxin reductase (TR), and superoxide dismutase (SOD) were determined spectrophotometrically in the mitochondria and cytosolic fractions. The expression of genes (Nrf2, Acc, Nqo1, and HmgCoa) were determined using quantitative RT-PCR. Results showed that AFB1 significantly increased mitochondrial cholesterol at day seven (treatment vs. control, p = 0.016). It also increased the concentrations of NO and MDA at day one and day seven while the activity of GPx and concentration of GSH were increased at day seven (p = 0.030) and day one (p = 0.025) alone, respectively, compared to control. The activities of cytosolic GR (p = 0.014), TR (p = 0.046) and GST (p = 0.044) were increased at day seven. AFB1 significantly increased the expression of Nrf2 (p = 0.029) and decreased the expression of Acc (p = 0.005) at day one. This study revealed that AFB1 disrupts hepatic mitochondrial lipids and antioxidant capacity. These changes were dependent on the timing of exposure and did not follow a linear time-course trend. These alterations could be part of the hepatic mitochondria response mechanism to acute AFB1 toxicity.

Gene Expression Profiling Analysis Reveals Putative Phytochemotherapeutic Target for Castration-Resistant Prostate Cancer.

Prostate cancer is the leading cause of cancer death among men globally, with castration development resistant contributing significantly to treatment failure and death. By analyzing the differentially expressed genes between castration-induced regression nadir and castration-resistant regrowth of the prostate, we identified soluble guanylate cyclase 1 subunit alpha as biologically significant to driving castration-resistant prostate cancer. A virtual screening of the modeled protein against 242 experimentally-validated anti-prostate cancer phytochemicals revealed potential drug inhibitors. Although, the identified four non-synonymous somatic point mutations of the human soluble guanylate cyclase 1 gene could alter its form and ligand binding ability, our analysis identified compounds that could effectively inhibit the mutants together with wild-type. Of the identified phytochemicals, (8'R)-neochrome and (8'S)-neochrome derived from the Spinach (Spinacia oleracea) showed the highest binding energies against the wild and mutant proteins. Our results identified the neochromes and other phytochemicals as leads in pharmacotherapy and as nutraceuticals in management and prevention of castration-resistance prostate cancers.

Oxidative Stress in Extrahepatic Tissues of Rats Co-Exposed to Aflatoxin B1 and Low Protein Diet.

Early life exposure to aflatoxin B1 (AFB1) and low protein diet through complementary foods during weaning is common in parts of Africa and Asia. This study evaluated the effect of co-exposure to AFB1 and low protein diet on the extrahepatic tissues of rats. Twenty-four three-week old weanling male albino rats were used for this study and were randomly assigned into four groups: group 1 served as control and was fed normal protein diet (20% protein), group 2 was fed low protein diet (5% protein), group 3 was fed normal protein diet + 40 ppb AFB1 while group 4 received low protein diet + 40 ppb AFB1, all for eight weeks. Afterward, biomarkers of anemia (packed cell volume (PCV), hemoglobin) and kidney function (urea, uric acid, and creatinine) were determined in the blood while biomarkers of oxidative stress were determined in the tissues spectrophotometrically. Co-exposure to AFB1 and low protein diet significantly (p < 0.05) decreased body weight gain and PCV, increased biomarkers of kidney functions and induced oxidative stress in the tissues studied. There was significant (p < 0.05) reduction in glutathione concentration while TBARS was significantly increased in the tissues. Co-exposure to AFB1 and low protein diet had additive effects on decreasing the weight gain and potentiation effect of kidney dysfunction in the rats. The co-exposure also decreased antioxidant enzymes and increased oxidant status in the tissues. Our results demonstrate that this co-exposure has deleterious health effects on extrahepatic tissues and should be a public health concern especially in developing countries where AFB1 contamination is common.

Naringin enhances reverse cholesterol transport in high fat/low streptozocin induced diabetic rats.

Naringin, a citrus-derived flavonoid with antihyperglycemic, antihyperlipidemic, and antioxidant properties, is reported to be a useful nutraceutical in the management of diabetes and its complications. This study investigated the mechanism of antiatherogenic properties of naringin in type 2 diabetes (T2DM) using high fat-low streptozocin rat model of T2DM. Rats were treated daily with 50, 100 and 200 mg/kg naringin orally for 21days. Levels of biomarkers of T2DM, lipid profile and activity of paraoxonase (PON) were assayed spectrophotometrically. The levels of expression of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr), scavenger receptor class B member 1 (Scarb1), aryl hydrocarbon receptor (Ahr), hepatic Lipase (Lipc), and lecithin-cholesterol acyltransferase (Lcat) were assessed using relative reverse transcriptase polymerase chain reaction technique. Naringin treatment resulted in a dose-dependent significant (p < 0.05) decrease in the levels of plasma cholesterol and triglyceride from 84.84 ±â€¯1.62 to 55.59 ±â€¯1.50 mg/dL and 123.03 ±â€¯15.11 to 55.00 ±â€¯0.86 mg/dL, respectively, at 200 mg/kg naringin. In the liver, Scarb1 and Ahr were significantly (p < 0.05) upregulated at 200 mg/kg naringin while Lipc and Lcat were significantly (p < 0.05) upregulated by 50 mg/kg naringin. T2DM-induced decrease in PON activities in the plasma, liver and HDL was significantly (p < 0.05) reversed by 200 mg/kg naringin treatment. These genes play critical roles in reverse cholesterol transport and hence our results showed that the antiatherogenic property of naringin in T2DM involves enhancement of reverse cholesterol transport and PON activity.

Stevioside modulates oxidative damage in the liver and kidney of high fat/low streptozocin diabetic rats.

This study investigated the potential of stevioside to prevent oxidative DNA damage in the liver and kidney of type 2 diabetes mellitus (T2DM) using high fat-low streptozocin rat model. Rats were treated daily with 12.5, 25 and 50 mg/kg stevioside orally for 21 days. Levels of biomarkers of T2DM, lipid profile and oxidative stress were assayed spectrophotometrically. The DNA ladder assay method was used to assess DNA fragmentation in the liver and kidney while computational analysis was used to predict the mechanisms of antidiabetic properties of stevioside. Stevioside significantly (p < 0.05) decreased the levels of plasma glucose, insulin, dipeptidyl peptidase IV and activities of kidney angiotensin converting enzyme. Stevioside significantly reduced oxidative stress by decreasing the levels of lipid peroxidation and nitric oxide in the liver and kidney; thereby, reducing the extent of DNA fragmentation in the liver and kidney of the diabetic rats. The in silico analysis showed that the ability of stevioside to exert these effects is linked to its inhibition of beta-adrenergic receptor kinase and G-protein-coupled receptor kinase. The results of this study suggest that the prevention of DNA fragmentation may be an additional benefit of the use of stevioside in the management of T2DM.

Acute aflatoxin B1 - Induced hepatotoxicity alters gene expression and disrupts lipid and lipoprotein metabolism in rats.

In this study, alterations in lipid metabolism associated with acute aflatoxin B1 (AFB1) induced hepatotoxicity and gene expression changes underlying these effects were investigated. Rats were orally administered three doses (0.25 mg/kg, 0.5 mg/kg and 1.0 mg/kg) of AFB1 for seven days; after which blood was collected and liver excised. Lipid profiles of plasma and liver were determined spectrophotometrically while the expression of genes associated with lipid and lipoprotein metabolism was assayed by reverse transcriptase polymerase chain reaction. Acute exposure to AFB1 increased the levels of plasma and liver cholesterol, triglycerides and phospholipids. AFB1 at 0.5 mg/kg and 1.0 mg/kg resulted in a dose-dependent (1.2 and 1.5 fold, respectively) downregulation of hepatic Cpt1a with a concomitant 1.2 and 1.5 fold increase in the level of plasma FFA, respectively. A similar observation of 1.2 and 1.3 fold increase was also observed in plasma triglyceride concentration, at both respective doses. AFB1 also decreased the relative expression of Ahr, Lipc and Lcat whereas, it upregulated Scarb1 in a dose dependent manner. AFB1-induced dysregulation of the expression of lipid and lipoprotein metabolizing genes may be one mechanism linking AFB1 to altered lipid metabolism and ultimately risk for coronary heart disease.

Persistence of acidosis in alloxan-induced diabetic rats treated with the juice of Asystasia gangetica leaves.

BACKGROUND: Diabetes mellitus is gradually becoming a global health burden leading to an increase in the search for herbal hypoglycemic agents as alternatives to synthetic ones. Asystasia gangetica is one of the herbs used in folklore system of medicine for managing hypoglycaemia associated with diabetes. MATERIALS AND METHODS: The influence of the juice of A. gangetica leaf on alloxan-induced diabetic rats was assessed by treating diabetic rats with 25%, 50% and 75% fresh juice and glibenclamide for 5 weeks. Afterwards, the plasma concentrations of glucose, triacylglycerols, total cholesterol, high-density lipoprotein (HDL) cholesterol, thiobarbituric acid reactive substances and bicarbonate were assayed spectrophotometrically. RESULTS: Treatment of the diabetic rats with the juice significantly (P < 0.05) reduced the elevated plasma levels of glucose to a level not significantly (P > 0.05) different from that of glibenclamide. The juice also significantly (P < 0.05) reduced the plasma lipid peroxidation and improved the lipid profile, as indicated by a significant (P < 0.05) reduction in the total cholesterol: HDL cholesterol ratio. However, there was a significant (P < 0.05) rise in the level of bicarbonate as result of the juice treatment from 28.15 ± 2.82 mmol/l in normal control to 60.83 ± 17.46 mmol/l in diabetic control and to 122.20 ± 34.68 mmol/l, 120.95 ± 35.09 mmol/l and 115.85 ± 11.79 mmol/l in 25%, 50% and 75% juice, respectively. CONCLUSION: Therefore, this inability of A. gangetica to prevent acidosis detracts from the potential of its usefulness in managing diabetes.